OP0258 RISK OF INCIDENT GOUT ASSOCIATED WITH INITIATION OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS VERSUS OTHER SECOND-LINE AGENTS AMONG METFORMIN USERS WITH TYPE 2 DIABETES
Authors: C. Yokose, N. Mccormick, L. Lu, J. Wei, Y. Zhang, H. Choi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Sodium-Glucose Cotransporter Type 2 Inhibitors (SGLT2i) are a revolutionary second-line treatment for type 2 diabetes associated with lower risk of cardiovascular and all-cause mortality, heart failure, and chronic kidney disease progression. Many trials have also found SGLT2i lower serum urate levels. However, data on gout risk are limited and the few available prior studies were not specific to those using metformin, the primary target populations of recent landmark trials like GRADE. <h3>Objectives</h3> To emulate recent clinical trials and compare incident gout risk among metformin-treated patients with type 2 diabetes initiating SGLT2i versus second-line type 2 diabetes treatments (glucagon-like peptide-1 receptor agonist [GLP1RA], dipeptidyl peptidase 4 inhibitors [DPP4i] or sulfonylureas). <h3>Methods</h3> We performed a new user, active comparator, population-based cohort study using administrative health data for nearly all residents of British Columbia, Canada from Jan 2014 to June 2022, including all dispensed prescriptions, regardless of funder. A cohort of adults with type 2 diabetes using metformin (first-line therapy) was identified from ICD codes and dispensing data. Primary outcome was incident gout, defined as inpatient or outpatient diagnosis of gout plus dispensing of a gout medication within 14 days, and no prior recorded gout diagnosis. We also stratified by sex, age, and baseline diuretic use. Cox proportional hazards models were used with propensity score overlap weighting. To evaluate reproducibility and for spurious associations, we also assessed for risk of genital infection (for which we expected SGLT2i would have a positive association), and for the risk of any osteoarthritis encounter, a negative control outcome for which we expected a null association. <h3>Results</h3> Hazard ratio (HR) for incident gout associated with SGLT2i initiation was 0.54 (95% CI: 0.39, 0.74) vs. DPP-4i (among n=27,791 type 2 diabetes patients), 0.39 (0.24, 0.62) for SGLT2i vs. GLP1RA initiation (n=19,875 patients), and 0.61 (0.46, 0.80) for SGLT2i vs. sulfonylurea initiation (n=71,625 patients) (<b>Table 1</b>). Results were consistent regardless of sex or age or baseline diuretic use. For control outcomes, SGLT2i initiators had higher risk of genital infection, as expected, while there was no difference in risk of osteoarthritis (<b>Table 1</b>). <h3>Conclusion</h3> SGLT2i initiation among metformin-treated patients with type 2 diabetes was associated with substantially lower risk of incident gout (i.e., primary prevention), compared with initiation of any other second-line options. Along with its known urate-lowering, as well as cardiovascular and survival benefits, SGLT2i could reduce risk of incident gout substantially for diabetes patients who need second-line agent after metformin. <h3>Reference</h3> [1]GRADE Study Research Group, <b>NEJM 2022;387:1075-88</b> <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Chio Yokose: None declared, Natalie McCormick: None declared, Leo Lu: None declared, Jie Wei: None declared, Yuqing Zhang: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart, Grant/research support from: Ironwood and Horizon.